Production of polymer fibres having nanoscale morphologies

ABSTRACT

The invention relates to porous fiber comprising a polymeric material, said fiber having a diameter of 20 to 4 000 nm and pores in the form of channels extending at least to the core of said fiber and/or through said fiber.  
     The process for producing the porous fiber comprises electrospinning a 5 to 20% by weight solution of at least one polymer in an organic solvent using an electric field above 10 5  V/m to obtain a fiber having a diameter of 20 to 4 000 nm and pores in the form of channels extending at least to the core of said fiber and/or through said fiber.  
     The porous fiber may be used as a carrier for a catalyst, as an adsorbent or absorbent or as a biomaterial, may be chemically modified or functionalized or may be used as a template for producing highly porous solids.

[0001] This invention relates to a process for producing nanoscalepolymeric fibers having morphologies and textures, especially havingopen porous structures, and also their modification and use.

[0002] Owing to their high surface/volume ratio and their differences totypical ordering structures in macroscopic systems, nanoscale materials-have special physical and chemical properties, described for example inGleitner, H.; “Nanostructured Materials” in Encyclopedia of PhysicalScience and Technology, Vol. 10, p. 561 ff. These include short-rangemagnetic properties in the case of metallic or oxidic materials, easyfield-induced tunneling of electrons from filament tips, or particularlyadvantageous biocompatibilities due to nanoscale microdomains. Thesedifferences in property profiles compared with macroscopic materialshave led to technological innovations in microelectronics, displaytechnology, surface technology, catalyst manufacture and medicaltechnology, especially as carrier materials for cell and tissuecultures.

[0003] Fiber materials having filament diameters of less than 300 nm, infact down to a few 10 nm, are useful, if electroconductive, as fieldelectron emission electrodes according to WO 98/1588. They similarlyoffer technological benefits in semiconductor systems as described inU.S. Pat. No. 5,627,140 and also as catalyst systems having improvedactivity profiles, described in WO 98/26871. Such fibers can bechemically modified and be provided with chemical functions, for exampleby chemical etching or by plasma treatment, processed into woven fabricsor compacted into feltlike materials. They can be incorporated, not onlyin unorganized form but also in an aligned or organized form as wovens,drawn-loop knits, formed-loop knits or in some other compactedarrangement, into macroscopic construction material systems in orderthat mechanical or other physical properties of the materials ofconstruction may be improved.

[0004] According to WO 00/22207, fibers having diameters of less than 3000 nm can be produced using compressed gases expanding from specificnozzles. Prior art also includes electrostatic spinning processesdescribed in DE 100 23 456.9. GB 2 142 870, for example, describes anelectrostatic spinning process for manufacturing vascular grafts.

[0005] Nanofibers can be used as templates for coatings applied to thefibers from solutions or by vapor deposition for example. This makes itpossible to deposit on the fibers not only polymeric, ceramic, or oxidicor glassy materials but also metallic materials in the form ofuninterrupted layers. By dissolving, vaporizing, melting or pyrolyzingthe inner, polymeric template fiber it is thus possible to obtain tubesin a wide variety of materials of construction whose inner diameter canbe varied from 10 nm up to a few μm, depending on the filament diameter,and whose wall thicknesses are in the nm or μm range, depending oncoating conditions. The production of such nano- or mesotubes isdescribed in DE 10 23 456.9.

[0006] For certain applications of nanoscale fibers it appears to beadvantageous to create a large surface area using porous materials. InWO 97/43473, fibers are provided with a porous coating. A subsequentpyrolysis treatment provides high-porosity fibers that are advantageousfor catalytic uses for example.

[0007] The above-described processes for producing porous nano- andmesoscale fibers require plural steps and are time and cost intensive.Furthermore, porous fiber materials offer additional technical benefitsover uninterrupted, solid fibers, since they have a substantially largersurface area. True, nanotubes have a very large surface area, but arevery inconvenient to produce because of the pyrolysis step.

[0008] EP 0 047 795 describes polymeric fibers having a solid core and aporous, foamy sheath surrounding the core. The fiber core is said topossess high mechanical stability, while the porous sheath has a largesurface area. Yet in the case of very surface-active applications, forexample filtrations, the porous structure created according to EP 0 047795 is frequently inadequate.

[0009] It is an object of the present invention to provide nano- andmesoscale polymeric fibers having a very large surface area using asimple process. This object is achieved by porous fiber comprising apolymeric material, the fiber having a diameter of 20 to 4 000 nm andpores in the form of channels extending at least to the core of thefiber and/or through the fiber.

[0010] The invention further provides a process for producing porousfiber from a polymeric material, which comprises electrospinning a 3 to20% by weight solution of a polymer in a volatile organic solvent orsolvent mixture using an electric field above 10⁵ V/m to obtain a fiberhaving a diameter of 20 to 4 000 nm and pores in the form of channelsextending at least to the core of the fiber and/or through the fiber.

[0011] Electrospinning processes are described for example in Fong, H.;Reneker, D. H.; J. Polym. Sci., Part B, 37 (1999), 3488, and in DE 10023 456.9.

[0012] Field strengths vary from 20 to 50 kV, preferably from 30 to 50kV, and linear spinning speeds (exit speed at spinneret) from 5 to 20m/s, preferably from 0.8 to 15 m/s.

[0013] Porous fiber structures according to the invention comprisepolymer blends or copolymers, preferably polymers such as polyethylene,polypropylene, polystyrene, polysulfone, polylactides, polycarbonate,polyvinylcarbazole, polyurethanes, polymethacrylates, PVC, polyamides,polyacrylates, polyvinylpyrrolidones, polyethylene oxide, polypropyleneoxide, polysaccharides and/or soluble cellulose polymers, for examplecellulose acetate.

[0014] These polymers may be used individually or in the form of theirblends. In a particular embodiment of the invention, said polymericmaterial comprises at least one water-soluble polymer and at least onewater-insoluble polymer.

[0015] A blend of water-soluble and water-insoluble polymers may have ablending ratio in the range from 1:5 to 5:1 and preferably equal to 1:1.

[0016] In processes according to the invention, 3-20% by weight,preferably 3-10% by weight, particularly preferably 3-6% by weight, ofat least one polymer are dissolved in an organic solvent and electrospuninto a porous fiber. The fibers of the invention have diameters from 20to 1 500 nm, preferably 20 to 1 000, particularly preferably 20 to 500,most preferably 20 to 100 nm.

[0017] The volatile organic solvent used may be dimethyl ether,dichloromethane, chloroform, ethylene glycol dimethyl ether, ethylglycolisopropyl ether, ethyl acetate or acetone or a mixture thereof with orwithout further solvents. The vaporizing step may be carried out atatmospheric pressure or else under reduced pressure. If necessary, thepressure shall be adapted to the boiling points of the solvents.

[0018] It is advantageous to use solvents or solvent mixtures in theprocess which are a theta solvent for the polymer/polymer blend inquestion. The polymer solutions may also pass through the theta stateduring the electrospinning process. This is the case for example duringthe vaporizing of the solvent.

[0019] For polymer solutions in the theta state see Elias, H. G., inPolymer Handbook, IIIrd Ed., John Wiley & Sons, 1989; section VII.

[0020] These solutions are spun by electrospinning. Typically a polymersolution is continually pumped into spinnerets or, in the lab, into aspray cannula whose diameter is not more than 0.5 mm in the case of theapparatus available. The field strengths between cannula andcounterelectrode may be 2×10⁵ V/m and the distance may reach 200 mm.This produced uniform fibers having diameters from 20 to 4 000 nm, ascan be seen in the scanning electron micrograph of FIG. 1. Instabilitiesmay also lead to irregular thick places on the as-spun filaments. Thesurprising regular morphology, which is characterized by open pores,becomes apparent in the enlargements of FIGS. 2 to 5. The production ofthe porous polymeric nano- and mesofilaments is illustrated in theexamples.

[0021] The porous fibers of the invention have a large surface area ofabove 100 m²/g, preferably above 300 m²/g, especially above 600 m²/g,and most preferably above 700 m²/g. These surface areas can becalculated from dimensions derived from scanning electron micrographs ormeasured by the BET nitrogen adsorption method.

[0022] The porous fibers produced by the process of the invention can beprocessed into wovens, drawn-loop knits and shaped and also structuredpressed stock; wet-chemically and plasma-chemically modified; or loadedwith materials having different objectives, for example pharmaceuticallyactive entities or catalytic precursors, by impregnating and subsequentdrying.

[0023] The porous fibers of the invention may further be used as ad- orabsorbents, in the biological sector (biomaterial) and also as templatesfor producing highly porous solid articles (for example ceramics bycasting and burning out the polymeric templates).

[0024] The porous fibers of the invention may further be subjected tosurface modification using a low temperature plasma or chemicalreagents, for example aqueous sodium hydroxide solution, inorganicacids, acyl anhydrides or halides or else, depending on the surfacefunctionality, with silanes, isocyanates, organic acyl halides oranhydrides, alcohols, aldehydes or alkylating chemicals including thecorresponding catalysts. Surface modification may be used to confer onthe porous fibers a more hydrophilic or hydrophobic surface, and this isadvantageous for use in the biological or biomedical sector.

[0025] Porous fibers according to the invention can be used asreinforcing composite components in polymeric materials of construction,as filter materials, as carriers for catalysts, for example as ahydrogenation catalyst after coating of the pores with nickel, or forpharmaceutically active agents, as a scaffolding material for cell andtissue cultures and for a wide variety of implants where, for example,osseointegration or vascularization are used structurally. Epitheliumcells are thereby readily cultivable on porous polystyrene fibers. It issimilarly possible to apply osteoblasts to porous polylactide carriersand to grow a cell tissue by differentiation.

[0026] A further surprising effect is the anisotropy of the porousfibers according to the invention, which is identifiable by theirbirefringence. They are therefore particularly useful as a reinforcingcomponent in fiber composites, where the large internal surface areaprovides effective bonding and strength for the polymer matrix,especially after suitable surface modification.

[0027] In another embodiment of the invention, ternary mixtures of twopolymers, of which one is water soluble, for examplepolyvinylpyrrolidone, polyethylene oxide, polypropylene oxide,polysaccharides or methylcellulose, and a volatile solvent or solventmixture is spun. These ternary solutions were electrostatically spun inthe same manner as the binary mixtures recited above. Nano- andmesofibers were formed, but they did not possess porous morphology. Anonporous structure is obtained for the fiber when conventionalelectrospinning processes are used. It is advantageous in conventionalelectrospinning processes to use polymer solvents that are remote fromthe theta state and do not pass through it during the spinning process.

[0028] Only after a water treatment at elevated temperatures, which ledto the water-soluble polymer component being dissolved out, did thefiber materials exhibit a porous morphology comprising channel poresextending at least to the fiber core and/or through the fiber; seescanning electron micrographs in FIG. 6.

[0029] This fiber material too can be processed into wovens, drawn-loopknits and formed and also structured pressed articles; surficiallymodified and also functionalized; and be directed to the hereinaboverecited uses.

[0030] The examples which follow illustrate the production of ultrathin,cylindrical porous fibers according to the invention.

PRODUCTION EXAMPLE 1

[0031] Partly crystalline poly-L-lactide (PLLA) having a glasstransition temperature of 63° C., a melting temperature of 181° C. andan average molecular weight of 148 000 g/mol (manufacturer: BöhringerIngelheim, Germany) was dissolved in dichloromethane (FLUKA, Germany;chromatography grade). The concentration of the polymer in the solutionwas 4.4% by weight.

[0032] The metering rate of the solution to the outlet cannula, whichhad an internal diameter of 0.5 mm, was varied between 0.3 and 2 cm³/s.The temperature of the solution had been set to 25° C.

[0033] The distance between cannula tip and counterelectrode was between10 and 20 cm, while the operating voltage had been set to 35 kV.

[0034] The spinning process produced porous fibers having diameters from100 nm to 4 μm, depending on the metering rate. Scanning electronmicrographs (recorded on CamScan 4) show uniformly shaped fibers, asdepicted in FIG. 1, which reveal the continuous, open porous structureat higher REM resolution (FIG. 2). Not only the ellipsoidal poreopenings, which are oriented in the spinning direction and have sizesfrom 100 to 400 nm in the direction of the fiber axes and from 20 to 200nm in the transverse direction, but also examination of the fibers undera polarizing microscope (Zeiss MBO 50 including a rotatable polarizer)indicate appreciable anisotropy on the part of the porous fibermaterials produced in this way.

[0035] The BET surface areas of these porous fibers were between 200 and800 m²/g; calculation of the surface area from the scanning electronmicrographs even revealed surface areas of up to 1 500 m²/g.

[0036] The scanning electron micrograph of FIG. 3 illustrates a porousPLLA fiber produced at a metering rate of 0.8 cm³/s for the solution.The BET surface area of this fiber was measured at 650 m²/g, while thevalue calculated from the scanning electron micrograph was 1 200 m²/g.

PRODUCTION EXAMPLE 2

[0037] An aromatic polyurethane (Tecoflex™ from Thermetics, USA) havingan average molar mass of 180 000 g/mol was dissolved in acetone (FLUKA,Germany; chromatography grade) in a concentration of 6% by weight. Thetemperature of the solution had been adjusted to 23° C.

[0038] The electrostatic spinning conditions were the same as those ofproduction example 1. The anisotropic porous filaments which were againobtained had diameters ranging from 120 nm to 4 μm and a BET surfacearea between 150 and 600 m²/g.

[0039] The scanning electron micrograph of FIG. 4 illustrates suchpolyurethane filaments which were obtained at a metering rate of 1.2cm³/s (BET:

[0040]490 m²/g)

PRODUCTION EXAMPLE 3

[0041] A 13% by weight solution of polycarbonate having an averagemolecular weight of 230 000 g/mol in dichloromethane as per productionexample 1 was electrostatically spun at a feed temperature of 20° C. anda metering rate of 1.5 cm³/s. The electric field strength was 30 kV/m.

[0042]FIG. 5 illustrates a thus produced fiber, whose pores arecharacterized by distinctly smaller diameters. The fiber porosity was250 m²/g. On the basis of calculations, performed using pore andfilament dimensions taken from the scanning electron micrograph it hasto be assumed that pores extend at least into the filament core.

[0043] The same process according to the invention was used to process asolution of 7.5% by weight of polyvinylcarbazole in dichloromethane intofilaments under the same conditions. The results were similar to thoseof polycarbonate spinning.

[0044] The production example which follows illustrates the productionof ultrathin porous fibers from blends of water-insoluble andwater-soluble polymers.

PRODUCTION EXAMPLE 4

[0045] Atactic amorphous poly-D,L-lactide (PDLLA) having an averagemolecular weight of 54 000 g/mol and a glass transition temperature of52° C. (manufacturer: Böhringer Ingelheim, Germany) andpolyvinylpyrrolidone having an average molecular weight of 360 000 g/mol(K90; FLUKA, Germany) were dissolved in dichloromethane in weight ratiosof 5:1, 1:1 and 1:5. The polymer blend concentrations in dichloromethanewere between 2 and 5% by weight.

[0046] The electrode separation was 23 cm and the operating voltage 40kV. The metering rates range from 0.5 to 2 cm³/s.

[0047] Filaments were obtained with diameters from 80 nm to 4 μm thatdid not show any porosity whatever in a scanning electron micrograph.

[0048] The water-soluble polyvinylpyrrolidone (PVP) can be completelydissolved out of the thus produced fibers or out of webs fabricatedtherefrom, by treatment with water below room temperature. PVP removalwas complete after just 15 minutes of ultrasonication.

[0049]FIG. 6 shows by way of example the scanning electron micrograph ofa porous fiber produced in this way from a mixture of 5:1 PVP:PDLLA,whose BET surface area was measured at 315 m²/g.

[0050] The PVP/PDLLA ratios of 1:1 and 1:5 produced in that orderdecreasing porosities with BET surface areas of 210 m²/g and 170 m²/g.

[0051] The porous filaments produced according to the invention aredepositable as random coils. Given a suitable geometry for thecounterelectrode, sheetlike or ribbony arrangements of the as-spunfibers are producible as well.

Use Example 1

[0052] Coiled porous fibers as spun in production example 1 wereuniformly packed into a cylindrical aluminum mold having a diameter of20 mm and a rim height of again 20 mm and compressed by hand to a depthof 5 mm. The compressed porous fibers were then compacted with amatching aluminum ram being applied with a compressive force of 30 kp at50° C. for a period of 15 minutes.

[0053] This produced flat round pressed articles from 200 to 600 μm inthickness, whose BET surface areas were not more than 15% below the BETsurface areas of the fibers used.

[0054] The porous fiber produced in production example 1 at a meteringrate of 0.8 cm³/s was similarly compressed in plural stages andcompacted in the last phase using a force of 60 kp being provided at 50°C. for 60 minutes. This produced a pressed article 1.2 mm in thicknesshaving a BET surface area of 380 m²/g.

[0055] The wettability of the pressed articles with water was average,the contact angle being between 45 and 58 degrees.

[0056] The plaque thus produced was used as an ad- and absorbent in alaboratory suction filter having a tight closure between the funnel andthe glass frit underneath. When 100 ml of a 0.1% sugar solution wasapplied and passed through just once, the sugar was completely retainedby the sorbent layer produced from the porous fibers of the invention.

Use Example 2

[0057] The coiled porous fibers produced as per production example 2were activated in a microwave plasma by the action of an argon/oxygenmixture.

[0058] The apparatus used, Hexagon, was obtained from Technics Plasma,Germany. The microwave power had been set to 300 W, the system pressurewas 0.02 bar, and the two gases each were continuously added by definedleak at a rate of 4×10⁻³ standard liter/min. The porous filaments hadbeen placed in the plasma apparatus in a horizontal, cylindrical rotaryglass drum which was open at one end and was turning at n=20revolutions/minute.

[0059] After plasma treatment, the activated porous filaments werestirred into an aqueous solution of 5% by weight of hydroxyethylmethacrylate (from Rohm, Germany), filtered off after a exposure time of15 minutes and dried at 50° C. under a water jet vacuum for 24 hours.

[0060] The fibers treated in the manner described above weresubsequently treated with UV rays while being repeatedly turned. The UVsource used was an arrangement of 4 Ultra-Vitalux lamps (from Osram,Germany). They were irradiated for 30 minutes at an average distance of20 cm from the source.

[0061] The fibers were subsequently washed in water and filtered. Thefiltrate was found not to contain any free hydroxyethyl methacrylate(detection limit: 200 ppm in water), so that virtually complete chemicalattachment of the hydroxyethyl methacrylate to the surface of the porousfibers can be assumed.

[0062] The pressed articles produced therefrom as per use example 1 hada BET surface area of 680 m²/g and were characterized by very goodwettability with water.

[0063] The pressed articles obtained from use examples 1 and 2 wereexamined for their characteristics with regard to living cells incollaboration with the Institute for Physiological Chemistry in theUniversity of Münster in Germany. To this end, the samples wereinoculated with human umbilical vein endothelial cells (HUVECs) andsubsequently examined for growth.

[0064] While the samples of use example 1, on application in 24microwell plates (Nunc, Denmark) for 5 days (37° C., 37% by volume ofCO₂ in the sterile room air), subsequently exhibited a HUVEC number of22 000 to 30 000 per cavity, samples of the compression moldings as peruse example 2 produced endothelial cell numbers of 45 000 to 60 000 percavity under the same conditions.

[0065] It was further determined that, in the case of samples of useexample 2, neither any DNA activation nor mRNA synthesis nor expressionof cell-typical proteins is reduced, altered or degenerated. The methoddescribed in use example 2 is suitable for converting porous fibersproduced according to the invention into cell- and tissue-compatiblebiomaterials.

Use Example 3

[0066] Fiber materials of production examples 2 and 3 were twisted andcompacted into yarns in a manner resembling the classic spinningprocess, for which the fibers were slightly moistened. The yarn materialobtained had a thickness of 0.3 to 0.4 mm and resembled wool fiber.After drying, the yarns expanded to a thickness of 0.6 to 1 mm.

[0067] This yarn material from the porous primary fibers of theinvention can be wound into bobbins and was processible into simplewoven fabric in the lab.

[0068] The use of adhesives, binders and strengthening crosslinkers forsurface-activated fibers (use example 2) improves not only theprocessibility of the fiber materials obtained from the primary fiber ofthe invention but also their tensile strength.

[0069] The fabrics produced in this way are particularly useful forproducing highly porous catalyst carriers, thermal insulating materials,absorbers and filters, as a scaffolding material in tissue engineeringand for blood vessel and bone implantology. The high porosities promotevascularization, augment not only the cell supply with nutrients butalso the disposal of metabolites and offer advantages with regard tocell differentiation and also osseofication and tissue integration.

Use Example 4

[0070] Fibers as per production examples 1 and 3 were exposed to anargon atmosphere containing nickel carbonyl (FLUKA) in a plasmaapparatus (from Eltro, Baesweiler, Germany) in a rotating glass drum asper use example 2 at a pressure of 15 Pa, a 2.45 GHz microwave power of2 kW, a pulse duration of 500 μs and a period of 2 s. The argon flowedat 5 I/h over nickel tetracarbonyl heated to 40° C. The feed lines tothe plasma chamber were temperature controlled at 100° C. to preventdeposits of Ni(CO)₄.

[0071] Following a treatment time of just 10 minutes the filaments hadbecome completely blackened by deposition of very fine metallic nickel.

[0072] The porous filaments thus treated were pressed into plaques 1 mmin thickness as per use example 1 and cut into 5 mm×5 mm squares. Thesewere subsequently supplementarily reduced with hydrogen in a temperaturecontrolled glass tube at 50° C. for 3 hours. The hydrogen flow rate was10 I/h.

[0073] Ethylene was then mixed in at the same temperature at a flow rateof 1 I/h and became completely hydrogenated to ethane.

What is claimed is:
 1. Porous fiber comprising a polymeric material,said fiber having a diameter of 20 to 4 000 nm and pores in the form ofchannels extending at least to the core of said fiber and/or throughsaid fiber.
 2. The porous fiber of claim 1 having a surface area ofabove 100 m²/g.
 3. The porous fiber of either of claims 1 and 2 whereinsaid polymeric material is a homopolymer, a copolymer or a polymerblend.
 4. The porous fiber of any of claims 1 to 3 wherein saidpolymeric material is selected from the group consisting ofpolyethylene, polypropylene, polystyrene, polysulfone, polylactides,polycarbonate, polyvinylcarbazole, polyurethanes, polymethacrylates,PVC, polyamides, polyacrylates, polyvinylpyrrolidones, polyethyleneoxide, polypropylene oxide, polysaccharides and soluble cellulosepolymers.
 5. The porous fiber of any of claims 1 to 4 wherein saidpolymeric material comprises at least one water-soluble polymer and atleast one water-insoluble polymer.
 6. The porous fiber of any of claims1 to 5 subjected to a surface modification using a low temperatureplasma or a chemical reagent.
 7. A process for producing porous fiberfrom a polymeric material, which comprises electrospinning a 5 to 20% byweight solution of at least one polymer in a volatile organic solvent orsolvent mixture using an electric field above 10⁵ V/m to obtain a fiberhaving a diameter of 20 to 4 000 nm and pores in the form of channelsextending at least to the core of said fiber and/or through said fiber.8. The process of claim 7 wherein one or more water-soluble polymers andone or more water-insoluble polymers are used.
 9. The process of eitherof claims 7 and 8 wherein said organic solvent or solvent mixture is atheta solvent for said polymeric material.
 10. The process of any ofclaims 7 to 9 wherein said solution of said at least one polymer is in atheta state or passes through a theta state during said electrospinning.11. The process of any of claims 7 to 10 wherein said porous fiber issubjected to a surface modification using a low temperature plasma or achemical reagent.
 12. The use of the porous fiber of any of claims 1 to6 as a carrier for a pharmaceutically active agent.
 13. The use of theporous fiber of any of claims 1 to 6 as a carrier for a catalyst. 14.The use of the porous fiber of any of claims 1 to 6 as a reinforcingcomposite component in a polymeric material of construction.
 15. The useof the porous fiber of any of claims 1 to 6 as an adsorbent orabsorbent.
 16. The use of the porous fiber of any of claims 1 to 6 as ascaffolding material for a cell or tissue culture.